The acquired immunodeficiency syndrome (AIDS) is a global pandemic with over 13 million human immunodeficiency virus (HIV)-infected individuals worldwide. A major focus within our laboratory has been on defining the unique epidemiologic, clinical, virologic and immunologic features of HIV-1 and HIV-2 infections in developing countries and in the U.S. In Zaire we demonstrated a 40% infection rate in female prostitutes with an estimated 10% annual seroincidence. In India we documented a rise in HIV infection among prostitutes from 7.3% to 38.6% and from 1% to 15% among STD clinic attendees over the past 3 years. Among patients attending STD clinics in Baltimore, a retrospective 10-year survey demonstrated a marked increase in HIV infection from 0.2 to 5.5%. Common to all three cohorts was the strong association of HIV infection among heterosexuals with recent genital ulcerative and non-ulcerative sexually transmitted diseases. Even among patients attending a U.S. inner-city emergency department, HIV infection increased from 6.0% to 11.3% over 4 years with a marked increase among young women, black males, and heterosexuals. In perinatal studies of over 500 children born to HIV-infected women, we documented a 28% perinatal transmission rate which correlated with depressed maternal CD4+ and elevated CD8+ lymphocyte counts, anemia, chorioamnionitis and funisitis. There was no association between the presence of neutralizing antibodies of the V3 loop of gp120 and perinatal transmission. We developed an algorithm utilizing two serologic assays, the immune complex dissociated-p24 antigen assay and the IgA assay, which could reliably diagnose perinatal infection after the first week of life with a sensitivity and specificity of 99%, respectively. In two separate cohorts in Brazil and Haiti, we documented that human T lymphotrophic virus type 1 (HTLV-1) infection may accelerate the clinical course of HIV infection despite modulating the increase in nonfunctional CD4+ lymphocytes. Additional studies are planned to further elucidate the immunologic modulation of HIV infection by co-infection with HTLV-1 infection in these cohorts.